In each animal species tested the major histocompatibility system (MHS) is a crucial determinant for transplantation and also provides genetic markers for genes regulating disease susceptibility, immune response, development, cell-cell interaction, and complement components; the human MHS (HLA) plays an analogous role. Non-MHS alloantigens in mice have also been useful markers of differentiation of function for lymphocyte subsets, however, there is scant evidence for the existence of human non-HLA lymphocyte alloantigens. The objectives of this research proposal are: a) To identify and characterize new polymorphic cell surface antigens in man for MHS and non-NHS loci. Murine hybridoma antibodies specific for human alloantigens will be produced for direct detection of allospecificities; monomorphic murine hybridoma antibodies will be used to detect allelic gene products extracted from cell membranes by use of new immunoelectrophoretic techniques, including native IEF gels; and feasibility of using human hybridoma alloantibodies will be evaluated. b) To develop new approaches to analyzing relations between disease susceptibility and genetic markers. DNA restriction enzyme polymorphisms related to the HLA region of chromosome 6 will be identified and correlated with HLA antigens and disease susceptibility. New analytical statistical methods for demonstrating linkages between diseases and specific markers will be further developed and evaluated. c) To continue to maintain the current level of expertise in HLA typing participation in HLA workshops, characterization of local alloantisera and definition of HLA epitope maps with hybridoma antibodies will continue. The proposed studies will permit a more effective use of lymphocyte markers in studying genetic control of human disease and immune responses, and lymphocyte subsets, and the specific markers identified will be tested as a tool for disease classification, prognosis, and elucidation of pathogenesis; and will ultimately serve as a tool for eventual cloning of disease susceptibility genes and their products.